Survival of Bacterial Biofilms within Neutrophil Extracellular Traps Promotes Nontypeable Haemophilus influenzae Persistence in the Chinchilla Model for Otitis Media

Survival of Bacterial Biofilms within Neutrophil Extracellular Traps Promotes Nontypeable Haemophilus influenzae Persistence in the Chinchilla Model for Otitis Media
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DOI:
10.1159/000205937
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发表时间:
2009-01-01
影响因子:
5.3
通讯作者:
Swords, W. Edward
Swords, W. Edward
中科院分区:
医学2区
文献类型:
--
作者:
Hong, Wenzhou;Juneau, Richard A.;Swords, W. Edward

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非分型流感嗜血杆菌(NTHi)是急性和慢性中耳炎的主要致病因素,是世界范围内的主要公共卫生问题。在慢性和复发性中耳炎感染期间,NTHi的持续存在涉及中耳腔内形成的多细胞生物膜群落。细菌生物膜抵抗免疫清除和抗生素治疗,部分原因是包裹在聚合物基质中。在这项研究中,研究了生物膜在体内对细菌持续存在的贡献以及在实验性中耳炎过程中NTHi生物膜基质的组成。栗鼠中耳室内生物膜的存在与中耳积液和组织中细菌负荷的增加显著相关。薄片检查显示,多形核细胞位于含有弹性蛋白酶和组蛋白的DNA晶格中,这与中性粒细胞细胞外陷阱的定义一致。在整个生物膜的DNA晶格中发现了具有生物膜表型的活的多细胞生物膜群落。此外,NTHi在体外通过促进生物膜形成的脂寡糖部分抵抗吞噬细胞和细胞外中性粒细胞的杀伤。这些数据支持NTHi颠覆中性粒细胞胞外陷阱在体内持续存在的结论。这些数据还表明,可能需要对生物膜进行更全面的定义。版权所有(C)2009 S.Karger AG,巴塞尔
Nontypeable Hoemophilus influenzae (NTHi) is a leading cause of acute and chronic otitis media, which are a major public health problem worldwide. The persistence of NTHi during chronic and recurrent otitis media infections involves multicellular biofilm communities formed within the middle-ear chamber. Bacterial biofilms resist immune clearance and antibiotic therapy due in part to encasement within a polymeric matrix. In this study, the contribution of biofilms to bacterial persistence in vivo and composition of the NTHi biofilm matrix during experimental otitis media were investigated. The presence of biofilms within the chinchilla middle-ear chamber was significantly correlated with increased bacterial load in middle-ear effusions and tissue. Examination of thin sections revealed polymorphonuclear cells within a DNA lattice containing elastase and histones, which is consistent with the definition of neutrophil extracellular traps. Viable multicellular biofilm communities with biofilm phenotypes were found within the DNA lattice throughout the biofilm. Further, NTHi was resistant to both phagocytic and extracellular neutrophil killing in vitro by means of lipooligosaccharide moieties that promote biofilm formation. These data support the conclusion that NTHi subverts neutrophil extracellular traps to persist in vivo. These data also indicate that a more inclusive definition for biofilms may be warranted. Copyright (C) 2009 S. Karger AG, Basel